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At least 73 records · Page 4Linked to original sources

PubMed2003

Emerging concepts for the mechanism of alcoholic pancreatitis from experimental models.

The pathophysiologic mechanisms that underlie acute and chronic pancreatitis arising from alcohol abuse are poorly understood. The reasons for this state of knowledge result historically from a lack of models for experimental investigation. Ethanol feeding alone, even at high doses, has minimal and inconsistent effects on morphologic findings in the pancreas in experimental animals. This experience, plus the fact that alcohol abuse causes pancreatic pathology in only a minority of patients, suggest that ethanol acts to sensitize the pancreas to the deleterious effects of other stimuli. In this article, we discuss findings to support this concept of ethanol as a sensitizing agent and experimental models developed that can be used to investigate the effects of ethanol on the pathologic processes of pancreatitis. These pathologic processes include inflammation, cell death, intrapancreatic digestive enzyme activation, and fibrosis.

Animals↗

PubMed1985

The growing rabbit with a solitary, partially-obstructed kidney. Analysis of an experimental model with reference to the renal concentrating ability.

The systemic and renal effects of high partial ureteral obstruction were investigated in a new model of experimental hydronephrosis. The test group comprised 12 contralaterally nephrectomized growing male New Zealand rabbits. As compared to the pyelographic findings in 6 unilaterally nephrectomized control animals, the test group could be divided into partially obstructed but non-hydronephrotic and obstructed-hydronephrotic subgroups. Animals of all 3 groups were capable of increasing their weight during the first 2 postoperative months. The mean plasma creatinine concentration remained normal in the obstructed group and even hydronephrosis was compatible with a normal serum creatinine level. As studied during forced hypotonic expansion, the renal response to a vasopressin analogue was significantly different in all 3 animal groups. Reciprocal but less marked differences were noted in the animals' ability to retain water during this test. We conclude that in this experimental model the magnitude of the antidiuretic response is inversely related to the radiologically defined degree of obstruction.

Animals↗

PubMed2006

The spontaneously hypertensive rat: an experimental model of sulfur dioxide-induced airways disease.

Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation, and mucus hypersecretion, features that are common in bronchitis, emphysema, and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisposed spontaneously hypertensive (SH) rats display phenotypes such as systemic inflammation, hypercoagulation, oxidative stress, and suppressed immune function that are also apparent in COPD patients, we hypothesized that SH rat may offer a better model of experimental bronchitis. We, therefore, exposed SH and commonly used Sprague Dawley (SD) rats (male, 13- to 15-weeks old) to 0, 250, or 350 ppm sulfur dioxide (SO(2)), 5 h/day for 4 consecutive days to induce airway injury. SO(2) caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD rats. Increases in bronchoalveolar lavage fluid (BALF) total cells and neutrophilic inflammation were dose dependent and significantly greater in SH than in SD rats. The recovery was incomplete at 4 days following SO(2) exposure in SH rats. Pulmonary protein leakage was modest in either strain, but lactate dehydrogenase and N-acetyl glucosaminidase activity were increased in BALF of SH rats. Airway pathology and morphometric evaluation of mucin demonstrated significantly greater impact of SO(2) in SH than in SD rats. Baseline differences in lung gene expression pattern suggested marked immune dysregulation, oxidative stress, impairment of cell signaling, and fatty acid metabolism in SH rats. SO(2) effects on these genes were more pronounced in SH than in SD rats. Thus, SO(2) exposure in SH rats may yield a relevant experimental model of bronchitis.

Acetylglucosaminidase↗

PubMed2006

Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism.

The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 +/- 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 +/- 8.64 to 39.14 +/- 6.77 mmHg) and alveolar air (from 92.97 +/- 2.14 to 63.91 +/- 8.27 mmHg). The effective alveolar ventilation exhibited a significant reduction (from 199.62 +/- 42.01 to 84.34 +/- 44.13) consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio) also presented a significant reduction after embolization (from 0.96 +/- 0.34 to 0.33 +/- 0.17 fraction). The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 +/- 1.71 to 60.76 +/- 6.62 mmHg), but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 +/- 1.22 to 23.15 +/- 8.24 mmHg). Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 +/- 1.36 to 37.61 +/- 12.79 mmHg), as also did the calculated alveolar (from 56.38 +/- 22.47 to 178.09 +/- 37.46 mL) and physiological (from 0.37 +/- 0.05 to 0.75 +/- 0.10 fraction) dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution induced by hypocapnic bronchoconstriction.

Acute Disease↗

PubMed1985

The pathogenesis of acute pancreatitis. The source and role of oxygen-derived free radicals in three different experimental models.

Recent experimental work has suggested that oxygen-derived free radicals may play an important role in initiating the early capillary injury in acute pancreatitis. Data from models of ischemic injury in other organs have suggested the enzyme xanthine oxidase is important in generating oxygen-derived free radicals. The present study was performed to determine whether xanthine oxidase is the source of free radical production in experimental pancreatitis. Utilizing the isolated, perfused, ex vivo canine pancreas preparation, three models of pancreatitis were initiated with (1) free fatty acid infusion (FFA), (2) partial duct obstruction and secretin stimulation (POSS), and (3) ischemia (ISCH). In each model, during a 4-hour perfusion, edema developed, weight gain occurred (FFA 120.6 +/- 21.1 gm; POSS 44.5 +/- 6.9 gm; ISCH 63.3 +/- 14.0 gm), and the serum amylase became elevated (FFA 1827 +/- 397 u/dl; POSS 10,171 +/- 1487 u/dl; ISCH 1860 +/- 365 u/dl). When the xanthine oxidase enzyme inhibitor allopurinol was added to the perfusate prior to the 4-hour perfusion, edema formation was absent or minimal, weight gain was significantly less (FFA 15.2 +/- 2.5 gm p less than 0.05; POSS 8.8 +/- 2.7 gm p less than 0.001; ISCH 12.3 +/- 2.8 gm p less than 0.01), and the amylase remained normal or the elevation was significantly decreased (FFA 996 +/- 189 u/dl p less than 0.05; POSS 3021 +/- 1074 u/dl p less than 0.001; ISCH 993 +/- 214 u/dl p less than 0.002). These data confirm that oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis, and suggest that the enzyme xanthine oxidase may well be the source of their production.

Acute Disease↗

PubMed1994

Experimental models of arrhythmias: toys or truth?

In this communication two new experimental models of atrial fibrillation are described. One model (artificial maintenance of atrial fibrillation in conscious goats) points to the electrophysiological changes caused by prolonged atrial fibrillation. It shows that within 24 h of atrial fibrillation the atrial refractory period becomes markedly shortened and the duration of atrial fibrillation markedly prolonged. In the other model, experimentally induced atrial fibrillation in the dog is regionally entrained by local rapid pacing. However, termination of atrial fibrillation by local overdrive pacing was never observed. The possible implication of these new experimental models for prevention and treatment of clinical atrial fibrillation are discussed.

Animals↗

PubMedDate not supplied

[Experimental models of venous thrombosis].

Various experimental models have been developed in order to more clearly understand deep vein thrombosis, the mechanisms involved and its treatment. These models are based on venous stasis, either alone or combined with the injection of thrombogenic substances or endothelial lesions. Other models only use endothelial lesions. Thrombogenic substances are mostly composed of activated factor X or thrombin, which raises the problem of purity of the substances and determination of the antithrombotic activities of the substance tested, especially heparin and hirudin and their derivatives, and consequently their efficacy. Endothelial lesions can be induced by chemical, physical or electrical agents or by repeated application of clamps, or cellular crushing. These models result in the formation of various forms of venous thrombus. The development and improvement of experimental models is very important in every case. Experimental models of thrombosis constitute the best tool for the study of thrombosis, in which many points remain to be elucidated. They also allow the study and development of various antithrombotic substances the improvement of their efficacy. These models must be validated, standardized, reproductible and in agreement with local legislation in each country.

Animals↗

PubMed1981

[Pathology of cerebral edema. II. Experimental models and modifying agents].

Current experimental models of brain edema are described and evaluated for their contribution to the knowledge of basic processes involved in its production as well their contribution to the understanding of different clinical forms. The participation of each main pathogenic mechanism in a given experimental model is analyzed and proves to vary with each particular model and site studied. The importance of various experimental models in the evaluation of different therapeutic procedures directed to control the genesis and evolution of brain edema is stressed.

Animals↗

PubMed2005

Effect of orthotopic small bowel transplantation on mineral metabolism in an experimental model.

BACKGROUND: Numerous experimental models have been described for investigation of short bowel syndrome. The aim of this study was to examine the effect of orthotopic small bowel transplantation (OSBT) on universal metabolism in an inbred rat model, with particular emphasis on mineral metabolism. METHODS: Jejunoileal resection and syngeneic OSBT was performed in 12-week-old male Lewis rats. Metabolic studies were performed over the following 16 weeks. Bones were analysed by physicochemical methods, dual X-ray absorptiometry, biomechanical procedures and histomorphometry. Biochemical markers of bone turnover were also measured. RESULTS: Jejunoileal resection induced severe short bowel syndrome with profoundly reduced food efficiency, bone size, fracturing energy and bone mineral content, but no cancellous bone osteopenia. After OSBT rats showed normal growth; bones were of normal size, and bone mineral content and fracturing energy were similar to those in sham-operated controls. However, tibial, but not vertebral, cancellous bone osteopenia was found after transplantation. CONCLUSION: OSBT with portal venous drainage achieves almost optimal mineral and bone metabolism. In the absence of immunosuppressive therapy, OSBT does not appear to have major untoward side-effects on bone in rats.

Anastomosis, Surgical↗

PubMed1985

Intrinsic tendon healing. A new experimental model.

A new experimental model was developed to study intrinsic flexor tendon healing in vivo. Segment of flexor tendons from the synovial sheath region of rabbits' forepaw were cut, resutured and placed in a silicone tube, sealed in both ends with a GORE-TEX pericardial patch (pore-size less than 1 micron), fastened with silicone glue. The chamber was left subcutaneously in the back of rabbits for six weeks. At this time the chamber was filled with clear tissue fluid. Histologically and ultrastructurally the tendon demonstrated fibroplasia with cell proliferation and collagen synthesis in spite of the fact that no extrinsic cells could gain entrance into the chamber--a finding supporting the concept of intrinsic healing.

Animals↗

PubMed2000

Experimental models of migraine.

Experimental models have been developed to study various aspects of migraine. Here we describe the most commonly used models--mostly animal models--which led to the development of a pathophysiological concept of migraine. We focus on activation studies of the trigeminovascular system, the sphenopalatine ganglion, the superior sagittal sinus, the dura mater as well as blood vessels. The most common consequences of activation are noted and include protein extravasation, neuropeptide release, rCBF and diameter changes, c-fos expression and electrical neuronal activity. In addition, we briefly summarize the results of cortical spreading depression studies, as they relate to the human migraine aura. These models will continue to be useful to elucidate migraine pathophysiology and explore drug mechanisms.

Animals↗

PubMed2000

[Biological experimental models in orthopedics].

Experimental research in orthopedics is conducted on different experimental models. Animal models have to be characterized by high similarity and consistence of the animal bone tissue with human metabolism and must undergo similar biomechanical changes. This paper presents the advantages and disadvantages of the most commonly used animal models, with particular attention given to sheep.

Animals↗

PubMed1982

Arteriographic and ultrasonic evaluation of vascular clamp injuries using an in vitro human experimental model.

A new experimental model was developed for dynamic in vitro evaluation of clamp effects in normal and atherosclerotic human arteries. Five normal and 25 atherosclerotic arteries obtained at autopsy were perfused by a pulsatile blood pump. Five vascular clamps--DeBakey, Satinsky, Fogarty, bulldog and Potts--were applied separately to 150 arterial segments, 30 each. The arterial segments were examined by single exposure arteriography and real time ultrasonography. The arteries were opened longitudinally and examined for traumatic lesions and atherosclerotic plaques. Except for a single intimal tear, there were no lesions produced by the clamps applied to normal arteries. In atherosclerotic arteries, the number of traumatic lesions, intimal tears and flaps, was comparable for all five clamps except the bulldog clamp which caused no intimal flaps. Intimal tears and flaps were observed in 14 and 26 per cent of all atherosclerotic vessels, respectively. The occurrence of clamp trauma in atherosclerotic arteries was independent of the age, sex and direct clamp application to plaques. Sensitivity of intimal tears by arteriography and ultrasonography was comparable low. Intimal flap sensitivity and accuracy of ultrasonography were greater than that of arteriography, p less than 0.01. It is concluded that the occurrence of important trauma by vascular clamps in atherosclerotic arteries is high and occurs whether or not discrete plaques are clamped. Clamp trauma is minimal in normal arteries. Imaging ultrasonography is superior to arteriography in detecting intimal flaps and can demonstrate the majority of intimal flaps produced by vascular clamps.

Adolescent↗

PubMed1998

Short- and intermediate-term carcinogenicity testing--a review. Part 2: available experimental models.

Numerous experimental protocols for short- and intermediate-term carcinogenicity assays have been available for many years. This paper surveys various of these test systems in rodents, fish species, non-vertebrates and avian embryos in ovo. The mouse skin tumour assay and the rat liver foci assay were used to introduce the basic concepts of short- and intermediate-term carcinogenicity testing in the previous part of the review. The focus of this second part of the review is on rodent assays for carcinogenicity testing in the lung, kidney, urinary bladder, pancreas, stomach, oral cavity, small intestine, colon, and on the possibility to combine several target organs in multi-organ models. The potential use of various fish species, non-vertebrates and hatching eggs for carcinogenicity testing is outlined and the advantages and limitations are discussed. This review also presents the problem of validation of any carcinogenicity test system and proposes a strategy for contemporary safety assessment of chemicals with regard to the detection and evaluation of carcinogenicity.

Animals↗

PubMed2002

Comparison of metabolic responses to deep hypothermic total circulatory arrest and retrograde cerebral perfusion in an experimental model.

An experimental study was designed to search the effectiveness of retrograde cerebral perfusion which is presently used as cerebral protection method for the surgery of arcus aorta. Twelve dogs were subjected to the study. Six of them were remained in total circulatory arrest at 20 degrees C for 60 min. Retrograde cerebral perfusion was done again at 20 degrees C for 1 h for the other six dogs. Tumor necrosis factor (TNF), P-selectin, Intracellular Adhesion Molecule (ICAM), Creatine Phosphokinase (CPK-BB) and tissue Adenosine triphosphate (ATP) levels were measured, before the cardiopulmonary bypass at 37 degrees C and during perfusion period at 5, 60 min and 4 h. Tissue ATP level for retrograde cerebral perfusion group was 3.99+/-0.7 mcmol/g tissue and 2.86+/-0.1 mcmol/g tissue for total circulatory arrest group at fourth hour (p<0.05). TNF level was significantly higher in total circulatory arrest group than retrograde cerebral perfusion group (p<0.05). The samples taken at fourth hour of reperfusion showed the TNF level was, 162.55+/-13.1 pcg/ml for total circulatory arrest group and this value was 12.5+/-3.4 pcg/ml for retrograde cerebral perfusion group.ICAM (Intracellular Adhesion Molecule) level was higher in total circulatory arrest group (18.75+/-3.6 ng/ml) when compared to retrograde cerebral perfusion group (8.75+/-1.8 ng/ml) (p<0.05). All parameters showed that retrograde cerebral perfusion preserved the brain functions better comparing with total circulatory arrest. The time necessary for aortic surgery may be provided by the retrograde cerebral perfusion technique.

Adenosine Triphosphate↗

PubMed1978

Immune-complex mediated colitis in rabbits. An experimental model.

An experimental colitis in rabbits is described, following the intravenous injection of preformed immune complexes of human serum albumin (HSA) and anti-HSA into non-sensitised rabbits. Tissue damage was localised to the colon by the Auer technique of inducing local non-specific inflammation, by the rectal instillation of dilute formalin. Formalin alone gave transient changes that reverted to normal within 24 hours. In rabbits given intravenous immune complexes formed in antigen-excess, a severe colitis was initiated, with histological features including mucosal ulceration, mixed inflammatory cell infiltration in the lamina propria, and crypt abscess formation. It is possible that immune-complex damage may be one of the pathogenic mechanisms involved in human ulcerative colitis.

Animals↗

PubMed1987

Cardiac cryolesions as an experimental model of myocardial wound healing.

The standard coronary ligation model for experimental myocardial infarction results in variable areas and patterns of necrosis; therefore, the healing of such infarctions is also variable. The authors developed an experimental myocardial injury model using simple cryoinjury, which allows standardization of the size, depth, and location of the wound. Thirty-eight left ventricular cryolesions were created in 19 dogs, which were then killed from 3 to 35 days after injury. A consistent decrease in the depth of scar (p less than 0.005) and accumulation of collagen (p less than 0.0001) over time characterized this healing myocardial wound. Histologic examination revealed that the cellular pattern of healing myocardial cryolesions is similar to that of a healing myocardial infarction but with less variability. The authors advocate the use of cardiac cryolesions as a model of experimental myocardial wound healing.

Animals↗

PubMedDate not supplied

Experimental models in interventional neuroradiology.

Various experimental models have been developed to test interventional neuroradiologic techniques. Most have been used to test various devices and embolic materials, and a small number of models have been designed for teaching or training purposes. Experimental models in endovascular techniques have seldom been used to stimulate disease processes in order to facilitate their understanding.

Animals↗